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Disease Profile

Neu Laxova syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Antenatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

NLS; 3-phosphoglycerate dehydrogenase deficiency, neonatal form; Neu-Laxova syndrome

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases;

Summary

Neu Laxova syndrome (NLS) is a genetic disorder affecting many parts of the body. Babies born with NLS usually grow poorly during pregnancy (intrauterine growth restriction). At birth, they may be small (low birth weight and short in length) and their facial features are usually different and distinct. The babies may have a small head (microcephaly), sloping forehead, and widely spaced eyes (hypertelorism). Babies with NLS may also have extra fluid (edema) in their hands and feet, brain abnormalities, and rigid, stiff muscles. Other birth defects may affect the baby's arms, legs, skin, genitals, kidneys, and heart. Not every baby with NLS will have every sign or symptom of NLS.[1][2][3][4]

Neu Laxova syndrome (NLS) is caused by changes or mutations in one of three different genes, PHGDH, PSAT1, PSPH. The mutations cause too little L-serine (an amino acid) to be made. There must be a mutation in both copies of one of these genes, which means NLS is inherited in an autosomal recessive manner. NLS can be diagnosed both prenatally by an ultrasound or after birth. The diagnosis is suspected by signs and symptoms, but may be confirmed by genetic testing (prenatally by chorionic villi sampling (CVS) or amniocentesis; after birth by genetic blood test).[1][2][3][4] There is no cure or treatment for NLS at this time, but L-serine supplementation may prove to be an effective treatment in the future if the NLS is found early during a pregnancy.[3][4]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Ichthyosis
0008064
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Lack of skin elasticity
0100679
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Sloping forehead
Inclined forehead
Receding forehead

[ more ]

0000340
Thick vermilion border
Full lips
Increased volume of lip
Plump lips
Prominent lips
Thick lips

[ more ]

0012471
30%-79% of people have these symptoms
Abnormality of the philtrum
0000288
Absent septum pellucidum
0001331
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Aplasia/Hypoplasia involving the skeletal musculature
Absent/small skeletal muscles
Absent/underdeveloped skeletal muscles

[ more ]

0001460
Broad foot
Broad feet
Wide foot

[ more ]

0001769
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Dandy-Walker malformation
0001305
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
Depressed nasal ridge
Flat nose
Recessed nasal ridge

[ more ]

0000457
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
External genital hypoplasia
Underdevelopment of external reproductive organs
0003241
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypogonadism
Decreased activity of gonads
0000135
Large hands
large hand
0001176
Macrogyria
0007227
Macrotia
Large ears
0000400
Muscle spasm
0003394
Muscular dystrophy
0003560
Opisthotonus
0002179
Pachygyria
Fewer and broader ridges in brain
0001302
Polyhydramnios
High levels of amniotic fluid
0001561
Polymicrogyria
More grooves in brain
0002126
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Trismus
Lockjaw
0000211
5%-29% of people have these symptoms
Abnormal eyelash morphology
Abnormal eyelashes
Abnormality of the eyelashes
Eyelash abnormality

[ more ]

0000499
Abnormal nasolacrimal system morphology
0000614
Abnormality of cardiovascular system morphology
0030680
Arthrogryposis multiplex congenita
0002804
Bifid uvula
0000193
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Micromelia
Smaller or shorter than typical limbs
0002983
Osteomalacia
Softening of the bones
0002749
Osteopenia
0000938
Osteoporosis
0000939
Prominent occiput
Prominent back of the skull
Prominent posterior skull

[ more ]

0000269
Pterygium
0001059
Pulmonary hypoplasia
Small lung
Underdeveloped lung

[ more ]

0002089
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw

[ more ]

0000278
Rickets
Weak and soft bones
0002748
Scoliosis
0002650
Spina bifida
0002414
Submucous cleft hard palate
0000176

Cause

Neu Laxova syndrome (NLS) can be caused by mutations in three different genes, PHGDH, PSAT1, and PSPH. The syndrome is currently classified in type 1 and type 2 when caused by mutations in the genes PHGDH and PSAT1, respectively. The mutations in PSPH causing NLS have not yet been classified as a different type.[1][2][3]

These 3 genes, PHGDH, PSAT1 and PSPH, are the instructions (code) for making the enzymes needed to make the amino acid L-serine. L-serine has important functions in the body. Since L-serine is an amino acid, it is one of the building blocks used to make many different proteins our body needs. It is also used to make other important compounds needed throughout our body and helps the brain develop normally.[1][2][3]

Neu Laxova syndrome (NLS) can be considered as part of a group of diseases known as “serine biosynthesis defects”.[1] Serine biosynthesis defects result from different mutations in the PGDH, PSAT, or PSPH genes that lead to serine deficiency throughout the whole body (systemic). The serine biosynthesis diseases include:[2][4]

  • Neu-Laxova syndrome the most severe form
  • Infantile serine biosynthesis deficiency intermediate form with growth deficiency, small head, brain malformations, severe developmental delay, and severe neurological problems including seizures and stiff and rigid muscles (affects ability to move and develop speech).
  • Childhood serine biosynthesis disease the mildest form with normal growth and brain development, milder developmental delay, and seizures.

The difference between NLS and the other related syndromes is the amount of working protein that is made. In the case of NLS, the mutations in the genes do not allow very much working protein to be made at all. In other words, because of the mutation, one of the enzymes needed to make L-serine is almost completely inactive, so very little L-serine can be made in the body.[4]

Understanding that the symptoms of these diseases are caused by having too little L-serine is very important for future treatment, because giving L-serine before the neurological damage happens may be prove to be an effective therapy.[3][4]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Neu Laxova syndrome in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Neu Laxova syndrome. Click on the link to view a sample search on this topic.

References

  1. Darouich S, Boujelbene N, Kehila M, Chanoufi MB, Reziga H, Gaigi S & Masmoudi A. Neu-Laxova syndrome: Three case reports and a review of the literature. Ann Pathol. August, 2016; 36(4):235-244. https://www.ncbi.nlm.nih.gov/pubmed/27475004.
  2. Schanze D, Kariminejad A, Nordgren A, Kariminejad MH, Conner P, Grigelioniene G, Nilsson D, Nordenskjöld M, Wedell A, Freyer C, Wredenberg A, Wieczorek D, Gillessen-Kaesbach G, Kayserili H, Elcioglu N, Ghaderi-Sohi S, Goodarzi P, Setayesh H, van de Vorst M, Steehouwer M, Pfundt R, Krabichler B, Curry C, MacKenzie MG, Boycott KM, Gilissen C, Janecke AR, Hoischen A, & Zenker M. Neu-Laxova Syndrome Is a Heterogeneous Metabolic Disorder Caused by Defects in Enzymes of the L-Serine Biosynthesis Pathway. American Journal of Human Genetics. September 4 2014; 95(3):285-293. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157144/.
  3. El-Hattab AW, Shaheen R, Hertecant J, Galadari HI, Albaqawi BS, Nabil A & Alkuraya FS. On the phenotypic spectrum of serine biosynthesis defects. J Inherit Metab Dis. May, 2016; 39(3):373-81. https://www.ncbi.nlm.nih.gov/pubmed/26960553.
  4. El-Hattab AW. Serine biosynthesis and transport defects. Mol Genet Metab. July 2016; 118(3):153-9. https://www.ncbi.nlm.nih.gov/pubmed/27161889.
  5. Ugras M, Kocak G &, Ozcan H.. Neu-Laxova syndrome: a case report and review of the literature. J Eur Acad Dermatol Venereol. October, 2006; https://www.ncbi.nlm.nih.gov/pubmed/16987270.
  6. Neu-Laxova syndrome. Orphanet. October, 2006; https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=2439.

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